Cutaneous reactions to chemotherapeutic agents.

The task of evaluating a cutaneous eruption in the patient receiving chemotherapy can be quite formidable. Most of the time, these patients are receiving a multitude of agents and have profound immunosuppression. These factors may alter the more common manifestations of cutaneous eruptions. This article presents some of the more common cutaneous eruptions that may occur in an oncology patient receiving chemotherapy. It is hoped we may recognize clinical patterns seen with chemotherapeutic agents in the immunosuppressed population and, by recognizing these cutaneous eruptions, we may avoid the pitfalls of discontinuing medicines that may certainly be needed or altering the treatment course in a patient.

Posttransplant primary cutaneous T-cell lymphoma.

A patient with posttransplant cutaneous lymphoma is described. Although most posttransplant lymphomas are of B-cell origin, this patient's lymphoma is a primary cutaneous lymphoma of T-cell origin. Another report exists of the first case of posttransplant primary cutaneous T-cell lymphoma localized to the lower extremities. Our patient's involvement was generalized with tumor nodules on the face and anterior chest. Reduced immune surveillance, chronic antigenic stimulation caused by transplant grafts, and the direct oncogenic effects of immunosuppressive drugs have all been suggested as mechanisms. Prompt recognition of this condition and initiation of appropriate therapy with reduction of high-dose immunosuppression can lead to better patient outcomes.

Atypical cutaneous lymphocytic infiltrate and a role for quantitative immunohistochemistry and gene rearrangement studies.

AIM: To help clarify the significance of the T-cell receptor (TCR) gene rearrangement and its relationship to the immunophenotyping of histologically atypical cutaneous T-cell lymphoid infiltrates (ACLIs). MATERIALS AND METHODS: One hundred and twenty-four patients presented with lesions clinically suspicious for cutaneous T-cell lymphoma (CTCL). The average age was 55.8 years with a mean follow-up duration of 26.2 months. Cases were classified as malignant (64 cases), inflammatory dermatosis (28 cases), and indeterminate (32 cases), based on follow-up data and histopathology. Quantitative immunophenotyping with computer-assisted imaging was performed using immunohistochemical stains of anti-CD3, CD4, CD5, CD7, CD8, CD20, CD30, CD56, CD68, Bcl-2, p53, and proliferating cell nuclear antigen (PCNA). RESULTS: Abnormal immunophenotypic expression in 87.5% of the malignant cases, including CD4 or CD8 predominance (67%), deletion of pan-T-cell antigens (16.1%), and activation of antigen/oncogene expression (47%), was observed. In addition, 36 clinically malignant cases displayed rearranged bands by polymerase chain reaction (PCR) with TCR beta and gamma. Two benign cases displayed abnormal immunophenotype and two others showed rearranged bands. All of these patients responded to topical steroid therapy with complete resolution. Nineteen indeterminate cases displayed either rearranged bands or immunophenotypic abnormalities, 15 of which were reclassified as malignant. All but three patients improved after CTCL treatment. CONCLUSION: Quantitative immunophenotyping and gene rearrangement analysis can provide detailed information for classifying ACLIs with 91% diagnostic sensitivity and 87% specificity.

Propylthiouracil hypersensitivity: report of two patients with vasculitis and review of the literature.

Two patients with a hypersensitivity vasculitis in association with propylthiouracil (PTU) administration are described. Although both patients presented with a cutaneous eruption, our first patient suffered severe systemic manifestations and the second patient's involvement was primarily limited to the skin. Patients with a vascular hypersensitivity reaction to PTU typically present with constitutional symptoms, acral purpuric skin lesions, and variable involvement of multiple organ systems. The reaction is treated by urgent withdrawal of PTU and implementation of supportive measures and immunosuppressive agents, as necessary. Prompt recognition of this condition and initiation of appropriate therapy lead to complete recovery in most cases.

Chronic myelogenous leukemia and porphyria cutanea tarda in a patient with limited systemic sclerosis.

Systemic sclerosis is uncommonly associated with hematologic malignancies. We report the case of a patient who had chronic myelogenous leukemia 3 years after the CREST variant of systemic sclerosis was diagnosed. She also later had porphyria cutanea tarda. The majority of patients who had hematologic malignancies after the diagnosis of systemic sclerosis proved to have either multiple myeloma or chronic lymphocytic leukemia. Hematologic malignancies may be found in patients with systemic sclerosis (either limited or diffuse).

Role of Borrelia burgdorferi in the pathogenesis of morphea/scleroderma and lichen sclerosus et atrophicus: a PCR study of thirty-five cases.

Morphea (localized scleroderma), and lichen sclerosus et atrophicus (LSA) share common features with acrodermatitis chronica atrophicans (ACA), a known chronic form of borreliosis. These include similar histologic findings such as diffuse dermal fibrosis. These observations have led several investigators to consider the possibility of Borrelia burgdorferi (Bb) as a common etiologic factor among all of these diseases. The aim of this study is to investigate the role of Bb in the pathogenesis of morphea and LSA, by assaying for its presence in lesional skin biopsies from patients with these diseases. We utilized the nested polymerase chain reaction (PCR) technique to selectively amplify a longer segment of a Bb-specific somatic gene, on DNA from paraffin-embedded, formalin-fixed tissues. The results revealed no Bb-specific DNA sequence in 28 specimens of morphea/scleroderma and 7 of LSA with varying stages of disease. Furthermore, confirmatory Southern blot of the PCR product, resulted in similar findings. These data seriously question the role played by this spirochete in the pathogenesis of morphea and LSA, at least in the southeastern part of the USA.

Vesiculobullous diseases with prominent immunologic features.

It may be very difficult to differentiate between the many bullous skin diseases. Clinical presentation and age of onset can sometimes be helpful. Consultation with a dermatologist may facilitate diagnosis and treatment. More often, information from skin biopsy and immunofluorescent studies, such as DIF, IIF, or split-skin DIF or IIF, is required to make the diagnosis. It is hoped that current investigative studies will elucidate the role of immunoreactants found within the dermoepidermal basement membrane zone in the pathogenesis of these blistering diseases.

Epidermolysis bullosa acquisita preceding the development of systemic lupus erythematosus.

In most cases of epidermolysis bullosa acquisita that occur in patients with systemic lupus erythematosus, the diagnosis of systemic lupus erythematosus is made before the development of blistering. We observed three patients with well-documented epidermolysis bullosa acquisita that developed several years before the onset of systemic lupus erythematosus. One patient was producing anti-U1RNP autoantibodies at the time epidermolysis bullosa acquisita was diagnosed, and all five produced this antibody during the systemic lupus erythematosus phase of their illness. In addition, in all five cases of epidermolysis bullosa acquisita with systemic lupus erythematosus antibodies to double-stranded DNA ultimately developed, and severe systemic lupus erythematosus and lupus nephritis developed in four patients. Sera from 15 other patients with epidermolysis bullosa acquisita without overt systemic lupus erythematosus were analyzed for systemic lupus erythematosus-related autoantibodies. Four patients were found to have at least one such autoantibody. These findings further document an association between epidermolysis bullosa acquisita and systemic lupus erythematosus and suggest that patients with systemic lupus erythematosus who present with epidermolysis bullosa acquisita may represent a subset of lupus erythematosus that puts the patient at increased risk for the development of more severe systemic illness. Patients presenting with epidermolysis bullosa acquisita, especially those who are black or Hispanic, should be monitored for the development of potentially life-threatening systemic lupus erythematosus.

Copper facilitated chemiluminescence from the sulfhydryl proteins: yeast alcohol dehydrogenase, spinach ferredoxin and metallothionein.

This paper describes a copper mediated formation of active oxygen, presumably O2, from the sulfhydryl proteins, yeast alcohol dehydrogenase spinach ferredoxin and rabbit liver metallothionein which, on the addition of cyanide in the presence of acetaldehyde, displays as a chemiluminescence. These studies may provide some insights into the mechanisms of copper toxicity and provide a sensitive assay for monitoring the presence of sulfhydryl groups.

Mitochondrial chemiluminescence elicited by acetaldehyde.

Acetaldehyde-dependent chemiluminescence has been found to be a sensitive technique for the study of superoxide and hydrogen peroxide formation in beef heart mitochondria. The system responds to ATP and antimycin A with increased emission intensities and to ADP and rotenone with decreased intensities, indicating that the chemiluminescence reflects the energy status of the mitochondrion. These effects are based on the ability of acetaldehyde to react with superoxide and hydrogen peroxide to form metastable intermediates which decay spontaneously with the emission of light. Additionally, these intermediates can react with cyanide to give alternative products which can also decay with the emission of light, the cyanide-evokable chemiluminescence. The interaction of acetaldehyde with mitochondria is complex because acetaldehyde can serve as a hydrogen source for NADH and as an inhibitor (at high concentration) of electron transport, and appears to be a reducing agent for a heat-stable site that autoxidatively generates HOOH from O2-.. Inasmuch as acetaldehyde is a metabolite of ethanol, this broad spectrum of reactivity may play a role in the hepatic and cardiac toxicity that is associated with alcoholism. The heat-stable site that generates HOOH from O2-. has been studied further and appears to contain vicinal dithiol which is primarily responsible for the cyanide-evokable chemiluminescence.

Carcinogens and dicumarol: opposite effects on rat liver NAD(P)H dehydrogenation.

The carcinogens, N-acetyl-aminofluorene, 7,12-dimethylbenzanthracene, 3,4-benzpyrene and 3-methylcholanthrene, increase the activity of the soluble enzyme D-T-diaphorase. This action is observed 24 h after the administration of these chemicals to rats. Dicumarol blocks this effect. Dicumarol does not inhibit the increase in activity of the microsomal aryl hydrocarbon hydroxylase system as elicited by 3,4-benz(a)pyrene and 3-methylcholanthrene. The functional significance of these findings and the possible role of cytosolic enzymic changes in chemical toxicity are discussed.

Rat liver post-microsomal D-T diaphorase: activation of the enzymes by two carcinogens.

The effects of two carcinogens (N-acetylaminofluorene and 7, 12-dimethylbenz(a)anthracene) on the rat liver soluble D-T diaphorase are reported in this communication. The activity of the enzyme is increased in 24 hours by both compounds tested in this study.